Abstract In its recent RFA-DE-16-007, the NIDCR emphasizes a need for new studies on Class V restoratives with the ultimate goal to develop new approaches/materials that would outperform glass ionomer cements (GICs) and/or resin- modified GICs, currently most frequently used for these restorations. The RFA calls for interdisciplinary research that would address the specific concerns stemming from generally deteriorated health of elderly population with reduced salivary flow and compromised periodontium. Our group has been on the fore-front of the research on polymeric, bioactive remineralizing dental materials based on amorphous calcium phosphate (ACP) for two decades. We have already successfully designed ACP polymeric materials capable of efficiently restoring lost tooth mineral via sustained release of calcium (Ca) and phosphate (PO4) ions. These materials were intended for base/lining, orthodontic and endodontic applications. In this submission, we propose to develop new, antimicrobial (AM) and remineralizing ACP composites which will physico-chemically, mechanically and biologically outperform the conventional Class V restoratives. We will build upon our understanding of ACP chemistry and solution thermodynamics as well as remineralizing ACP polymeric systems. We will add the AM functionality to ACP composites to make them a polyvalent tool for combating root caries. For that purpose, we will synthesize new AM monomers and fine-tune the resins to improve the polymerization shrinkage and control polymerization stress while attaining high degrees of vinyl conversion, minimize leachability of the unreacted monomers and/or degradation products and enhance bonding to dentin. The overall working hypothesis is that a concomitant, long-term AM and remineralizing function is attainable without impeding the critical physicochemical, mechanical and biological properties of composites. This hypothesis will be tested through the following Specific Aims (SAs): SA1 - Synthesis and validation of new AM monomers; SA2 - Synthesis and characterization of ACP filler; SA3 - Formulation, biocompatibility, physicochemical and mechanical evaluation of copolymers and composites; SA4 - AM activity of resins and composites, and SA5 - Remineralizing efficacy of composites. The proposed research will yield a prototype AM ACP composite for Class V restorations recommendable for testing in an animal study and/or clinical trial.